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  • 1.  Adding an alternative analytical method for particle size analysis

    Posted 02-Nov-2017 12:20
    Hi All,

    If an ANDA applicant proposes to add an alternative analytical procedure for particle size analysis as a post approval change, would this be considered a major change, moderate change or annual reportable?

    The 2004 guidance Changes to approved NDA or ANDA states that "Establishing a new regulatory analytical procedure including designation of
    an alternative analytical procedure as a regulatory procedure" or a change in regulatory analytical procedure that does not provide same or increased assurance of identity, strength, Quality, purity or potency would be considered a major change.

    The 2015 guidance Analytical procedures and method validation for drugs and Biologics states that "After approval, for an NDA or ANDA, the addition, revision or deletion of an alternative analytical procedure that provides same or increased assurance of the identity, strength, quality, purity or potency of the material being tested as the analytical procedure in the approved application, must be documented in the next annual report.

    It seems like a contradiction but I would appreciate any explanation to this.


    Thanks,
    Mehul

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    Mehul Govani RAC

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  • 2.  RE: Adding an alternative analytical method for particle size analysis

    Posted 03-Nov-2017 02:00
    ​Hi Mehul

    I would say there is no contradiction as addition of an alternate method is submitted as a major change in case the method is changed altogether and does not assure the same degree of identity, strength, Quality, purity or potency. for eg. you change the method from laser diffraction to sieve analysis.  
    However in case the method is based on same principle, and you are maintaining the same specification controls, with minor changes in the method, which does not compromise on identity, strength, Quality, purity or potency of the DS/ DP, then the change can be submitted as a minor/ AR change. Hope this helps.

    Regards

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    Sharry Arora
    Novartis Pharmaceuticals
    Hyderabad
    India
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    Original Message


  • 3.  RE: Adding an alternative analytical method for particle size analysis

    Posted 03-Nov-2017 09:20
    Thank you Sharry. As you mentioned below, say if the method is changing from sieve analysis to Laser Diffraction and comparability studies show that it assures same or better degree of identity, strength, Quality, purity or potency. Would it still be a major change?

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    Mehul Govani RAC
    Regulatory Affairs Manager
    PL Developments
    Westbury NY
    United States
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    Original Message


  • 4.  RE: Adding an alternative analytical method for particle size analysis

    Posted 05-Nov-2017 23:19
    ​Hello Mehul

    It would have been a major change (PAS) in case of switch to an inferior method e.g. laser diffraction to sieve analysis. And it would have been an AR change in case of switch to method based on same principle (please see section 4.3, page 10 https://www.fda.gov/downloads/Guidances/UCM217043.pdf). In your case as you are switching to another method based on different principle (e.g. sieve analysis to laser diffraction) and assuring same or better degree of identity, strength, Quality, purity or potency, it would go as CBE. I would attempt it as CBE-0.

    Best Regards
    Sharry

    ------------------------------
    Sharry Arora
    Novartis Pharmaceuticals
    Hyderabad
    India
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    Original Message


  • 5.  RE: Adding an alternative analytical method for particle size analysis

    This message was posted by a user wishing to remain anonymous
    Posted 06-Nov-2017 11:05
    This message was posted by a user wishing to remain anonymous

    Please be advised that section 4.3 page 10 is talking about changes to the currently approved regulatory method. The question as I understand it, a change/replacing to a new method requires PAS. As someone else pointed out, adding/deleting an alternate method, keeping the currently approved regulatory method can be filed as an annual report change. In other words, replacing from sieve analysis to laser diffraction & vice versa is not an AR.
    Original Message


  • 6.  RE: Adding an alternative analytical method for particle size analysis

    Posted 03-Nov-2017 09:30
    Hello Mehul,

    Following is the excerpt from the PAC-ATLS guidance:
    Under certain sections of 21 CFR 314.70 (e.g., 314.70(b)(2)(vi)), a change in analytical testing site is currently designated as a prior approval supplement. However, under 21 CFR 314.70(g)(2)(ii)(A), this type of change is a "Supplement-Changes Being Effected in 30 Days," absent extraordinary circumstances. This guidance is intended to implemented under 21 CFR 314.70(d) are used, (2) all postapproval commitments made by the applicant relating to the test method(s) have been fulfilled (e.g., providing methods validation samples), (3) the new testing facility has the capability to perform the intended testing, and (4) the new testing facility has had a satisfactory current good manufacturing practice (CGMP) inspection within the past 2 years.

    This change can be filed as a CBE30 if all the above 4 conditions are met.

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    Romita Mehta, MS, RAC
    Regulatory Affairs Manager
    Nostrum Laboratories, Inc.
    Kansas City, MO
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    Original Message


  • 7.  RE: Adding an alternative analytical method for particle size analysis

    Posted 03-Nov-2017 10:31

    The 2004 example is for establishing a new/alternate method as the regulatory method thereby replacing the original method.  The 2015 example describes adding/deleting/revising an alternate method which in this case the original method is still considered the regulatory method and therefore annual reportable since the original method is still the regulatory method and would be used in any dispute resolution.  In these instances I would always add the new method an alternate via annual report as long as there are no issues/concerns with the original regulatory method.

    Tom

    Chicago




    Original Message


  • 8.  RE: Adding an alternative analytical method for particle size analysis

    Posted 10-Nov-2017 11:48
    All PAS are based on the material attribute that changes the quality of the finished product.

    Few things to consider is as below:

    1) what material you are considering, its drug substance, excipients or in-process blend. It matters based on its impact on the final product, i.e. impact of drug substance is more than excipient.

    2) As in the start of the thread you asked only addition of the method, means you have sieve analysis and besides that you are adding Laser diffraction, so its more assurance and can be reported as Annual Report.

    3) Your second consideration from switching sieve analysis to laser diffraction, which require validation study as well and need to provide 3 lots of that material resulting data with both methods to assure the laser diffraction method is more assured compared to sieve analysis.

    4) Need to consider the material supplier (drug substance / excipients) for the laser diffraction method. If they are doing or not ? Its your initiative ? or its resulting query of one ANDA that affects to the other ANDA ?

    I hope by considering above facts you may determine your best strategy.

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    Gaurang Bhavsar, MS, RAC
    Scientist-II, R&D and RA
    Sunrise Pharmaceutical, Inc.
    Rahway, NJ 07065
    USA
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    Original Message


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